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The optimal hemoglobin threshold to guide red blood cell transfusion for patients with acute myocardial infarction and anemia is uncertain. This prespecified secondary analysis of the MINT (Myocardial Ischemia and Transfusion) trial, which randomly assigned patients to a liberal transfusion threshold versus a more restrictive threshold, used target trial emulation methods to compare 4 transfusion strategies to maintain patients' hemoglobin concentrations at or above thresholds of 10, 9, 8, or 7 g/dL. Visual Abstract. Effect of Four Hemoglobin Transfusion Threshold Strategies in Patients With Acute Myocardial Infarction and Anemia: The optimal hemoglobin threshold to guide red blood cell transfusion for patients with acute myocardial infarction and anemia is uncertain. This prespecified secondary analysis of the MINT (Myocardial Ischemia and Transfusion) trial, which randomly assigned patients to a liberal transfusion threshold versus a more restrictive threshold, used target trial emulation methods to compare 4 transfusion strategies to maintain patients' hemoglobin concentrations at or above thresholds of 10, 9, 8, or 7 g/dL. Background: The optimal hemoglobin threshold to guide red blood cell (RBC) transfusion for patients with acute myocardial infarction (MI) and anemia is uncertain. Objective: To estimate the efficacy of 4 individual hemoglobin thresholds (<10 g/dL [<100 g/L], <9 g/dL [<90 g/L], <8 g/dL [<80 g/L], and <7 g/dL [<70 g/L]) to guide transfusion in patients with acute MI and anemia. Design: Prespecified secondary analysis of the MINT (Myocardial Ischemia and Transfusion) trial using target trial emulation methods. (ClinicalTrials.gov: NCT02981407) Setting: 144 clinical sites in 6 countries. Participants: 3492 MINT trial participants with acute MI and a hemoglobin level below 10 g/dL. Intervention: Four transfusion strategies to maintain patients' hemoglobin concentrations at or above thresholds of 10, 9, 8, or 7 g/dL. Protocol exceptions were permitted for specified adverse clinical events. Measurements: Data from the MINT trial were leveraged to emulate 4 transfusion strategies and estimate per protocol effects on the composite outcome of 30-day death or recurrent MI (death/MI) and 30-day death using inverse probability weighting. Results: The 30-day risk for death/MI was 14.8% (95% CI, 11.8% to 18.4%) for a <10-g/dL strategy, 15.1% (CI, 11.7% to 18.2%) for a <9-g/dL strategy, 15.9% (CI, 12.4% to 19.0%) for a <8-g/dL strategy, and 18.3% (CI, 14.6% to 22.0%) for a <7-g/dL strategy. Absolute risk differences and risk ratios relative to the <10-g/dL strategy for 30-day death/MI increased as thresholds decreased, although 95% CIs were wide. Findings were similar and imprecise for 30-day death. Limitation: Unmeasured confounding may have persisted despite adjustment. Conclusion: The 30-day risks for death/MI and death among patients with acute MI and anemia seem to increase progressively with lower hemoglobin concentration thresholds for transfusion. However, the imprecision around estimates from this target trial analysis precludes definitive conclusions about individual hemoglobin thresholds. Primary Funding Source: National Heart, Lung, and Blood Institute. [ABSTRACT FROM AUTHOR]

Background: Frailty is associated with adverse cardiovascular outcomes independent of age and comorbidities, yet the independent influence of frailty progression on cardiovascular outcomes remains uncertain. Methods: To determine whether frailty progression is associated with adverse cardiovascular outcomes, independent of baseline frailty and age, we evaluated all Medicare Fee‐for‐Service beneficiaries ≥65 years at cohort inception with continuous enrollment from 2003 to 2015. Linear mixed effects models, adjusted for baseline frailty and age, were used to estimate change in a validated claims‐based frailty index (CFI) over a 5‐year period. Survival analysis was used to examine frailty progression and risk of adverse health outcomes. Results: There were 8.9 million unique patients identified, mean age 77.3 ± 7.2 years, 58.7% female, 10.9% non‐White race. In total, 60% had frailty progression and 40% frailty regression over median follow‐up of 2.4 years. Compared to those with frailty regression, when adjusting for age and baseline CFI, those with frailty progression had a significantly greater risk of incident major adverse cardiovascular and cerebrovascular events (MACCE) (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.31–1.31), all‐cause mortality (HR 1.34, 95% CI 1.34–1.34), acute myocardial infarction (HR 1.08, 95% CI 1.07–1.09), heart failure exacerbation (HR 1.30, 95% CI 1.29–1.30), ischemic stroke (HR 1.14, 95% CI 1.14–1.15). There was also a graded increase in risk of each outcome with more rapid progression, as well as significantly fewer days alive at home (DAH) with more rapid progression compared to the slowest progression group (270.4 ± 112.3 vs. 308.6 ± 93.0 days, rate ratio 0.88, 95% CI 0.87–0.88, p < 0.001). Conclusions: In this large, nationwide sample of older Medicare beneficiaries, frailty progression, independent of age and baseline frailty, was associated with fewer DAH and a graded risk of MACCE, all‐cause mortality, myocardial infarction, heart failure, and ischemic stroke compared to those with frailty regression. [ABSTRACT FROM AUTHOR]

The riverine transport and deposition of mud is the primary agent of landscape construction and evolution in many fluvial and coastal environments. Previous efforts exploring this process have raised uncertainty regarding the effects of hydrodynamic and chemical controls on the transport and deposition of mud, and thus the constructions of muddy coastal and upstream environments. As such, direct measurements are necessary to constrain the deposition of mud by river systems. Here, we combine laboratory evidence and a field investigation in the Mississippi River delta to explore the controls on the riverine transport and deposition of mud. We show that the flocculation of mud, with floc diameters greater than 10 μm, in freshwater is a ubiquitous phenomenon, causing the sedimentation of mud to be driven by changes in local hydrodynamics, and thus providing an explanation for how river systems construct landscapes through the deposition of mud in both coastal and upstream environments. Plain Language Summary: Muddy landscapes are some of the most common and vital environments on Earth's surface, such as floodplains, deltas, and estuaries. Due to their small size, and thus easily suspendable nature, mud particles are thought to be extremely difficult to deposit under typical flow conditions in rivers. As such, the means by which rivers deposit mud has been the subject of much study and debate. Canonically, the deposition of cohesive sediment occurs as rivers approach the ocean, where increases in salinity induce the aggregation of clay and silt particles to form heavier floccules, or "flocs." Recent studies have also explored the influence of organic material on mud aggregation. However, the means by which rivers are able to construct muddy landscapes upstream, in the absence of saline or organic‐rich water, remains uncertain. To address this discrepancy, we utilize a combination of laboratory evidence and a field investigation on the Mississippi River delta to show that all mud is transported as flocs, not as individual grains, and as such, the deposition of mud by river systems is controlled by the ability of the river flow to suspend existing mud flocs, and not by abrupt changes in water chemistry inducing flocculation in coastal regions. Key Points: Flocculation of mud in water is a ubiquitous phenomenonSalinity may have little to no effect on mud floc size as rivers enter marine environmentsDeposition of flocculated mud in river systems is driven by changes in hydrodynamic stress [ABSTRACT FROM AUTHOR]

Background Frailty is increasingly recognized as a useful measure of vulnerability in older adults. Multiple claims-based frailty indices (CFIs) can readily identify individuals with frailty, but whether 1 CFI improves prediction over another is unknown. We sought to assess the ability of 5 distinct CFIs to predict long-term institutionalization (LTI) and mortality in older Veterans. Methods Retrospective study conducted in U.S. Veterans ≥65 years without prior LTI or hospice use in 2014. Five CFIs were compared: Kim, Orkaby (Veteran Affairs Frailty Index [VAFI]), Segal, Figueroa, and the JEN-FI, grounded in different theories of frailty: Rockwood cumulative deficit (Kim and VAFI), Fried physical phenotype (Segal), or expert opinion (Figueroa and JFI). The prevalence of frailty according to each CFI was compared. CFI performance for the coprimary outcomes of any LTI or mortality from 2015 to 2017 was examined. Because Segal and Kim include age, sex, or prior utilization, these variables were added to regression models to compare all 5 CFIs. Logistic regression was used to calculate model discrimination and calibration for both outcomes. Results A total of 3 million Veterans were included (mean age 75, 98% male participants, 80% White, and 9% Black). Frailty was identified for between 6.8% and 25.7% of the cohort with 2.6% identified as frail by all 5 CFIs. There was no meaningful difference between CFIs in the area under the receiver operating characteristic curve for LTI (0.78–0.80) or mortality (0.77–0.79). Conclusions Based on different frailty constructs, and identifying different subsets of the population, all 5 CFIs similarly predicted LTI or death, suggesting each could be used for prediction or analytics. [ABSTRACT FROM AUTHOR]